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Safety, Feasibility, and Tolerability of Ten Days of At-Home, Remotely Supervised tDCS During Gamified Attention Training in Children with Acquired Brain Injury: An Open-Label, Dose-Controlled Pilot Trial
Get PDFBackground/Objectives: Chronic attention problems occur in approximately 25% of children after acquired brain injury (ABI). When delivered daily, transcranial direct current stimulation (tDCS) may improve attention; however, access to daily in-clinic tDCS treatment can be limited by other commitments, including concurrent therapy, school commitments, and caregiver schedules. Treatment access can be improved through home-based interventions, though these require several practical and safety considerations in a pediatric ABI population. This study evaluated the safety, feasibility, and tolerability of remotely monitored at-home tDCS during online gamified attention training in pediatric ABI. Methods: We conducted a randomized, single-blind, dose-controlled clinical trial of at home tDCS in Brisbane, Australia (10 tDCS sessions; 20 min; 1 mA or 2 mA; bilateral dorsolateral prefrontal cortex). Participants attended our clinic at baseline for clinical assessments, fitting of the personalized tDCS headband, and training in how to use tDCS at home. All sessions were remotely supervised using live videoconferencing. We assessed the feasibility and tolerability of at-home tDCS and our customized, personalized at-home tDCS headband as primary outcomes. As secondary outcomes, we evaluated changes in functional connectivity (fc) and reaction time (RT). Results: Seventy-three participants were contacted over six months (January-June 2023) and ten were enrolled (5 males; mean age: 12.10 y [SD: 2.9]), satisfying a priori recruitment timelines (CONSORT reporting). All families successfully set up tDCS and completed attention training with excellent protocol adherence. There were no serious adverse events over the 100 total sessions. Nine participants completed all stimulation sessions (1 mA: n = 5, 2 mA: n = 4). Participants in the 2 mA group reported greater tingling, itching, and discomfort (all p < 0.05). One participant in the 1 mA group was unable to complete all sessions due to tolerability challenges; however, these challenges were resolved in the second half of the intervention by gradually increasing the stimulation duration across the 10 days alongside additional coaching and support. Conclusions: Overall, daily remotely supervised at-home tDCS in patients with pediatric ABI is safe, feasible, and tolerable. Our results support larger, sham-controlled efficacy trials and provide a foundation for the development of safe and effective at-home stimulation therapeutics that may offer targeted improvement of neurocognitive symptoms in children
Sanitary inspection characteristics, precipitation, and microbial water quality - A three-country study of rural boreholes in Sub-Saharan Africa
Get PDFMicrobial contamination of drinking water contributes to disease burdens that disproportionately impact infants and children and are largely preventable through suitable design, operation, monitoring, and management of improved water systems. The World Health Organization (WHO) has published guidance on water safety planning, water quality monitoring, and management approaches, including recommendations on sanitary inspection (SI) of water systems to detect and manage microbial hazards associated with fecal contamination. SI is a low-cost risk assessment tool for water systems based on observable risk factors (RFs) associated with potential water safety hazards. While SI has been previously studied, much of the literature has not quantitatively explored rainfall interactions with SI risk as drivers of fecal contamination. We merged remote-sensing rainfall estimates with SI and water quality data collected from 966 rural boreholes in Ethiopia, Ghana, and Burkina Faso. Logistic regressions (binary and ordinal) were used to characterize associations of total SI score, as well as individual risk factors (RFs), and classes of RFs (i.e., “Source,” “Transport,” and “Barrier” risks) with fecal indicator bacteria (FIB) occurrence, controlling for rainfall (over the past 1–15 days before sampling). We found associations (P < 0.05, OR: 3.5, 95% CI 1.05-11.66) between SI scores and E. coli risk categories controlling for fifteen-day total rainfall. Furthermore, interactions between rainfall and risk factors in the “barrier” category, and the “transport” category were associated with E. coli occurrence. Several individual RFs were also significantly associated with microbial contamination. Incorporating precipitation into models improved model fit characteristics (improved Pseudo R squared and AIC value); specifically, accounting for cumulative rainfall during the fifteen days before sampling improved model fit (increased pseudo-R2 from 0.035 to 0.05) for E. coli contamination. These findings can inform design, construction, maintenance, and monitoring of boreholes and prompt timely remediation of defects in such systems, potentially enhancing water safety
The pan-variant potential of light: 425 nm light inactivates SARS-CoV-2 variants of concern and non-cytotoxic doses reduce viral titers in human airway epithelial cells
Get PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) prolonged the coronavirus disease 2019 (COVID-19) pandemic. The continued development of novel pan-variant therapeutics to treat currently circulating and future VOCs is critically important. Photomedicine may offer broadly applicable, pan-variant treatments. In this study, we show that visible light centered around 425 nm inactivates each of the five SARS-CoV-2 VOC lineages that have been identified by the World Health Organization (Alpha, Beta, Delta, Gamma, and Omicron) in cell-free suspensions in a dose-dependent manner, including bamlanivimab-resistant variants. Specifically, 60 J/cm2 of 425 nm light reduced SARS-CoV-2 titers by >4 log10 relative to unilluminated controls. We observed that 425 nm light inactivates SARS-CoV-2 through restricted entry to host cells. In addition, a non-cytotoxic dosing regimen of 32 J/cm2 of 425 nm light reduced infectious virus titers in well-differentiated air-liquid interface (ALI) human airway epithelial (HAE) cells infected with the Beta, Delta, and Omicron variants that incorporate mutations associated with immune evasion and/or increased transmissibility. Infectious SARS-CoV-2 titers were reduced when dosing began during the early stages of infection or in more established infections. Finally, we translated these findings to the RD-X19, a novel medical device that emits 425 nm light; our results showed that the RD-X19 restricted spike binding to ACE-2 and reduced SARS-CoV-2 titers in cell-free suspensions (by >2 log10) and in the ALI HAE model (by >1 log10). These findings indicate that photomedicine utilizing 425 nm visible light may serve as a novel, pan-variant treatment modality for COVID-19.IMPORTANCEThe continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of variants that can evade public health measures, including vaccines and therapeutics. Thus, the continued development of broadly applicable measures to supplement current public health measures and standards of care remains critical. Photomedicine is one such approach. In this study, we show that non-ultraviolet visible light can inactivate each SARS-CoV-2 variant of concern (VOC) by preventing entry to host cells. Furthermore, visible light reduced the amount of virus produced in an infection model of the human airway at multiple stages of infection, demonstrating the antiviral capability of visible light. This study provides preclinical support for the development of visible light to serve as a SARS-CoV-2 countermeasure and warrants further investigation
Alignment of PrEP adherence and HIV exposure risk among pregnant and postpartum women in Lilongwe, Malawi
Get PDFOBJECTIVE: When measured continuously, adherence to HIV pre-exposure prophylaxis (PrEP) is consistently low in studies of pregnant and postpartum women. We investigated how PrEP adherence aligned with HIV exposure risk. METHODS: We conducted a trial of a PrEP adherence support intervention in Lilongwe, Malawi. Pregnant women who met eligibility criteria for PrEP had visits at three and six months following enrollment. At each visit, HIV exposure risk was categorized as low or moderate/high (i.e., higher) risk based on an algorithm. PrEP adherence was measured via tenofovir concentrations, with functional adherence defined at levels consistent with ≥4 doses/week. HIV exposure risk and PrEP adherence were classified as either aligned (i.e., higher HIV risk/PrEP adherence, low HIV risk/PrEP non-adherence) or not aligned (i.e., higher HIV risk/PrEP non-adherence, low HIV risk/PrEP adherence). Probability differences (PD) were used to estimate the effect of the PrEP adherence intervention on aligned PrEP adherence. RESULTS: 164 women were included in the analysis. HIV exposure risk was higher for 81 participants (49%) at three months and 89 (54%) at six months. PrEP adherence was low at three months (34%) and at six months (29%). Aligned PrEP adherence was observed in 89 (54%) participants at three months and 83 (51%) at six months. 62% at higher HIV exposure risk were not aligned at month three, which increased to 68% at month six. The probability of aligned PrEP adherence was greater among those randomized to the intervention than those receiving standard of care at three months (PD:15.7%; 95%CI:0.8%, 30.6%). This was also evident in analyses that considered women with high HIV risk but low adherence. CONCLUSION: Alignment of PrEP adherence with HIV exposure risk was dynamic. PrEP adherence should be considered in the context of evolving HIV exposure risk during pregnancy and postpartum, with greater emphasis on periods of elevated HIV risk exposure
Mode of Patient Sexual Orientation and Gender Identity Disclosure and Receipt of Tailored Cancer Resources
Get PDFImportance: For lesbian, gay, bisexual, transgender, queer, questioning, and other (LGBTQ+) individuals with cancer, disclosing sexual orientation and gender identity (SOGI) in a safe clinical environment can improve survivorship outcomes and satisfaction. Although SOGI disclosure can facilitate patient-centered care, little is known about whether SOGI information is being used to improve care or how use may vary by mode of SOGI disclosure. Objective: To assess whether the mode of SOGI disclosure (self-disclosed, clinic collected, not disclosed, or other) is associated with receipt of clinical resources tailored to LGBTQ+ individuals among cancer survivors. Design, Setting, and Participants: This cross-sectional study uses data from the OUT National Cancer Survey, a web-based survey of LGBTQ+ adults with a history of cancer in the US, collected from September 2020 through March 2021. The study comprised a convenience sample of 2342 LGBTQ+ cancer survivors. Main Outcome and Measures: Multivariable logistic regression was used to assess the association between SOGI disclosure mode and receipt of at least 1 clinical resource tailored to LGBTQ+ individuals related to mental health, tobacco use, alcohol use, physical activity, or survivorship care. The primary exposure was mode of SOGI disclosure. Covariates included age, cancer type, current cancer status, and region. Results: This national sample of 2342 LGBTQ+ cancer survivors (mean [SD] age, 58.4 [16.7] years; 1428 assigned male at birth [61%]) included 79 Black participants (3%), 136 Hispanic participants (6%), 2019 White participants (86%), 64 multiracial participants (3%), and 90 participants of other race or ethnicity (4%). A total of 1394 participants (60%) identified as cisgender male, and 775 (33%) as cisgender female, and the most common sexual orientation was gay (1272 [54%]). Participants reported many cancer types, with genitourinary cancers being most common (523 [22%]). Most respondents (1798 [77%]) indicated that their care team knew their LGBTQ+ identity, with disclosure most often via self-disclosure (804 [34%]) or clinic collection (944 [42%]). Only 174 (7%) received an LGBTQ+ survivorship care plan, and 892 (38%) received at least 1 resource tailored to LGBTQ+ individuals. Compared with those with clinic-collected SOGI disclosure, those who did not disclose SOGI information (odds ratio [OR], 0.58 [95% CI, 0.44-0.78]) or who self-disclosed SOGI information (OR, 0.84 [95% CI, 0.69-1.02]) had lower odds of receiving any tailored resources. Conclusions and Relevance: In this cross-sectional study of SOGI disclosure and use, few LGBTQ+ cancer survivors received tailored clinical resources despite high rates of SOGI disclosure. Clinical use of SOGI information remained limited, especially when it was not collected systematically. Efforts should prioritize both safe SOGI data collection and its integration into patient-centered care
Exploring the Power and Possibility of Contextually Relevant Social Studies–Literacy Integration
Get PDFThe authors of this article describe a study designed to support first-grade students’ social studies knowledge and literacy development through a teacher–researcher co-constructed and teacher implemented integrated unit within the context of a rural community. The goals of the study were to determine the extent to which a contextually relevant unit of study affected the development of students’ content knowledge of key terms from the domain of social studies and influenced students’ reading and social studies interest. The researchers used a combined multi-phase and convergent mixed methods design, implementing a matched pairs design for the quantitative, quasi-experimental component of the study. Results indicated that assignment to the treatment condition was a predictor of students’ post implementation vocabulary scores and social studies interest. In pairing these results with the qualitative analyses of students’ end-of-unit retellings, researchers found that vocabulary can be a powerful bridge to cultural and content knowledge when the focus of instruction and texts is on local and community knowledge, demonstrating that contextually relevant social studies–literacy integration is a promising practice for building content knowledge and interest in first grade classrooms. Directions for future research are discussed
The MyCancerGene study: a hybrid type 1 effectiveness-implementation randomized study comparing a patient-centered digital genetic health portal to usual care after receipt of cancer genetic testing
Get PDFBackground Genetic testing has become more complex with the transition from single gene testing to multi-gene panels and whole-exome sequencing. The adoption of more complex genetic testing and the promise of precision medicine has created a critical and urgent need for longitudinal clinical follow-up with patients who undergo cancer genetic testing given the residual uncertainty. There is an increasing need for multidisciplinary translational research that focuses on how to advance precision medicine discoveries into clinical practice and to capitalize on connectivity (e.g. digital health) interventions in ways that optimize cancer risk reducing behaviors in real-world clinical populations. Methods The overall goal of this Hybrid Type 1 effectiveness-implementation randomized study is to evaluate the effectiveness of the MyCancerGene intervention to improve longitudinal (short-term and long-term) understanding (e.g. knowledge) and reactions to (e.g. anxiety) clinical genetic testing compared to usual care. We hypothesize that access to MyCancerGene will be associated with short-term and post-disclosure increases in knowledge, decreases in distress, increases in communication with relatives and health care providers and performance of risk reducing health behaviors compared to usual care. Equally important, we hypothesize that our implementation process evaluation will inform recommendations for future adaptation and sustainability for other precision medicine applications. Discussion Given the increasing complexity of genetic testing applications (e.g. multi-gene testing, whole exome sequencing) and the need for post-disclosure follow-up, we expect this study to inform evidence-based practice guidelines for delivery of genetic medicine and potentially change the paradigm to include longitudinal care in precision medicine. To address the clinically significant gap in the delivery of genetic medicine, patient and provider stakeholder input have been used to develop a patient and provider informed centered genetic digital health portal to enhance patient understanding of, and affective and behavioral responses to genetic testing, particularly in the era of evolving evidence and risk information. Trial registration This protocol was registered at clinicaltrials.gov (NCT04774445) in February 18, 2021. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-025-14968-2
Strengthening Access to NC Ferries to Support Coastal Community Resiliency, Health, and Mobility
Get PDFThis plan investigates barriers to multimodal access at ferry terminals in coastal North Carolina, focusing on how transportation infrastructure, service gaps, and demographic vulnerabilities shape mobility for rural communities. Using county-level demographic analysis, ferry terminal site evaluations, and plan content review, the project identifies challenges including limited transit integration, poor pedestrian and bicycle infrastructure, and high dependence on private vehicles. Developed as part of a broader research effort led by the UNC Highway Safety Research Center for the North Carolina Department of Transportation, this project provides targeted recommendations for improving terminal facilities, expanding mobility services, and integrating multimodal access into future transportation planning. By highlighting the role of first- and last-mile barriers, the findings offer insights for planners and policymakers seeking to strengthen rural mobility networks and better support underserved coastal populations.Master of City and Regional Plannin
Nicotinamide Counteracts the Detrimental Effect of Endothelin-1 on Uterine Decidualization During Early Pregnancy by Influencing EDNRB
Get PDFEndothelin-1 (ET-1) is involved in the pathogenesis of preeclampsia. Mice (Edn1H/+) having excess endothelin-1 developed preeclampsia-like phenotypes during pregnancy in a maternal genotype-dependent manner. Here, we investigated whether decidualization is impaired in Edn1H/+ dams, and whether nicotinamide (a potent inhibitor of ET-1) exerts beneficial effect. We compared implantation sites between wild type (WT) and Edn1H/+ dams with or without nicotinamide treatment. Implantation sites of Edn1H/+ dams exhibited abnormal ectoplacental cones and sinusoids, along with reduced vascular density in the mesometrial regions of the decidua. VEGF levels were higher in the decidua of Edn1H/+ dams compared with WT dams. Markers of decidualization were decreased in Edn1H/+ dams. Nicotinamide supplementation corrected this abnormality. During differentiation (decidualization) of cultured human endometrial stomal cells, ET-1 impaired the upregulated expression of decidualization markers. The effect of ET-1 was reversed by nicotinamide. These results show nicotinamide counteracts the detrimental effects of ET-1 on endometrial decidualization and has potential to improve embryo implantation and subsequent pregnancy outcomes
Simian Immunodeficiency Virus-Derived Extracellular Vesicles Induce a Chronic Inflammatory Phenotype in Healthy Astrocytes Unresolved by Anti-Retroviral Therapy
Get PDFBackground/Objectives: Extracellular vesicles (EVs) are key mediators of intercellular communication and are implicated in the neuropathogenesis of HIV-associated brain injury (HABI). However, their direct effects on glial cells, particularly in the context of antiretroviral therapy (ART), remain incompletely understood. Methods: In this study, we investigated how EVs from naïve, Simian Immunodeficiency Virus (SIV)-infected, and SIV-infected ART-treated rhesus macaques impact primary mixed glial cultures. Results: Through multiple, sequential applications mimicking chronic exposure, we found that EVs from SIV-infected animals significantly reduced glial expansion and induced a simplified, reactive astrocyte morphology indicative of neuroinflammatory stress. In contrast, EVs from naïve animals supported glial health. EVs derived from ART-treated animals provided partial protection from SIV-induced effects, yet still suppressed glial proliferation and failed to fully restore normal morphology. Furthermore, cytokine profiling revealed that both SIV and SIV + ART EVs induced a sustained proinflammatory secretory phenotype, characterized by elevated IL-6, IL-8, and IFN-γ. Conclusions: Our findings demonstrate that systemically circulating EVs in SIV infection are potential drivers of glial dysfunction. The persistence of these pathogenic EV effects despite ART suggests a vesicle-mediated mechanism that may contribute to chronic neuroinflammation and cognitive impairment in virally suppressed individuals